Prostate cancer is one of the most frequently diagnosed tumors, and the second leading cause of cancer death among men in the United States. There appears to be an important link between bioenergetics, apoptosis, and prostate carcinogenesis. Several studies propose that androgens and their receptors may act directly on the mitochondria to alter mitochondrial function during prostate carcinogenesis. Furthermore, reactive oxygen species production that apparently results from aberrant changes in mitochondrial function in prostate epithelial cells apparently drives tumorigenesis in the prostate. The indolent nature of prostate tumorigenesis strongly suggests that a chemopreventive strategy would be effective in preventing malignancy. Epigallocatechin-3- gallate (EGCG), the principal polyphenolic component in green tea catechins, has emerged as a promising prostate cancer chemopreventive agent. Green tea catechins (mainly EGCG) causes no biologically significant adverse side effects when relatively high doses are administered orally to humans, and a recent chemoprevention study showed that these EGCG-containing catechins were safe and very effective in suppressing the progression of prostate premalignant lesions to prostate cancer. In vitro observations suggest that the anticancer activity of EGCG may arise from its ability to engage cell death pathways (i.e., induce apoptosis) in premalignant and/or malignant prostate epithelial cells while sparing their normal counterparts. EGCG has also been shown to alter cellular redox homeostasis and/or disrupt mitochondrial function in tumor cells, which may be fundamental to its anticancer activity. These putative chemopreventive properties of EGCG have not been investigated extensively in transformed prostate epithelial cells. The proposed study will investigate the hypothesis: prostate epithelial cells representing various stages of prostate carcinogenesis (i.e., immortalized, tumorigenic, and malignant cells) exhibit marked changes in bioenergetic processes (i.e., oxidative phosphorylation) and redox status (i.e., reactive oxygen species production) compared to their normal counterparts. These bioenergetic and redox changes, perhaps in early-stage carcinogenesis, dictate sensitivity to apoptosis induction by the cancer chemopreventive agent EGCG. The hypothesis will be addressed by completing two specific aims: 1) compare and contrast the bioenergetic phenotypes of normal, premalignant, and malignant prostate epithelial cells in vitro with putative genetic changes (e.g., changes in androgen receptor, epidermal growth factor receptor, prostate-specific antigen, p53, Mn-SOD, and Bcl-2 protein expression) associated with prostate carcinogenesis in vivo;and 2) assessing the relative sensitivity to apoptosis induction by the cancer chemopreventive agent EGCG among normal, premalignant, and malignant prostate epithelial cells in vitro, and ascertain if there is a correlation between sensitivity to apoptosis induction, genetic prostate carcinogenesis signatures, and possible changes in mitochondrial function/redox status (e.g., oxygen consumption and reactive oxygen species production) in these cells.